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CRISPR-Cas9 is a new technology used to edit the genome (complete set of DNA) in any living organism—including humans.

Haven’t researchers been editing genomes already?

Yes, since the mid-1970s, scientists have been changing the DNA of living organisms. Researchers have traditionally used model organisms such as mice and fruit flies, as they are among the few species that come with an effective toolkit for genetic manipulation (i.e. shorter life cycles and large numbers of offspring). Using these techniques, however, it can take over a year to create new lines of genetically altered mice, as the editing of embryonic stem cells is inefficient.

Unlike alternative gene-editing techniques, CRISPR-Cas9 is cheap, quick, and easy to use. It outperforms older methods for gene editing, as it is easier to employ, has a high success rate, and is far more user-friendly to the average scientist.

In fact, Dr. Josiah Zayner, a former NASA researcher, created an Indiegogo campaign to sell do-it-yourself CRISPR kits, encouraging amateur scientists to try gene editing for themselves and claiming that his NASA lab could be replicated “on a kitchen table.”

CRISPR-Cas9 is allowing for research that would otherwise have required too much time or money to carry out. This technology is also not limited to a set of model organisms. Theoretically, it is possible to edit the genes of any living organism.

Where did CRISPR come from and how does it work?

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) are DNA sequences that are found in naturally-occurring bacterial immune system.

Bacteria can often be infected by viruses and the CRISPR immune system can be used to protect against these attacks through three main steps:

Adaptation – DNA fragments of the invading virus are incorporated into the CRISPR region of the bacteria’s genome

Synthesis of CRISPR RNA– The CRISPR sequence is transcribed to create small RNAs, each like a barcode specific to different viruses that the bacteria has seen before.

Targeting – A Cas nuclease (CRISPR-associated protein) can then bind these barcodes that function like a genetic GPS, guiding the nuclease to destroy the DNA of the invading viruses

In short, Cas proteins snip sequences of DNA, and CRISPR is a DNA sequence that tells Cas9 exactly where to snip. For more information on the mechanisms behind CRISPR-Cas9, click here.

How do researchers use CRISPR to edit specific genomes?

Before injecting the CRISPR system into a cell, researchers pre-program the guide RNA to match a designated target gene in a cell’s DNA. Once the guide RNA and Cas9 are injected into the cell, the two stay together, and the RNA directs Cas9 to a specific part of the DNA. (Note: Cas9 is one of many Cas proteins. It is the one that most researchers use as a tool in the lab, but many exist in different bacteria strains). Cas9 then snips out the targeted DNA sequence. Naturally, the cell immediately attempts to make repairs. Scientists can then rewrite the genetic code by adding an additional piece of DNA that the cell can use to repair the break. A faulty gene can then be repaired using the CRISPR-Cas 9 technology by providing a normal copy of the gene that the cell can use to repair.

Only a few days are required for a designed RNA guide sequence to arrive by mail. It takes a few months to complete the entire gene editing process using CRISPR-Cas9.

What are potential applications of this technology?

Interestingly, the dairy industry has actually been using CRISPR for several years, far before the gene editing revolution. Cheese and yoghurt manufacturers used CRISPR to create cultures better able to survive bacteriophage attacks, thereby avoiding food waste. However, this new capacity to manipulate genes quickly and precisely can be applied to develop new materials, biofuels, drugs and foods at low cost in little time. CRISPR-Cas9 technology is also anticipated to revolutionize military medical science and advance knowledge on therapy for infectious diseases, wound healing, and tissue regeneration.

Theoretically, CRISPR could be applied to treat any disease caused by genetic mutations. Though we now have the capacity to edit the genome, some diseases like Huntington’s disease, primarily affect the brain, which is difficult to access. Even if the tools are available, we

In cultured human cells and in mice, this technology has been applied to target Huntington’s disease, cystic fibrosis, sickle cell anemia, among many others. However, a significant amount of work must be done before moving CRISPR into the clinical setting.

Over the last two years, several companies have been formed to develop CRISPR-based gene therapy. Editas Medicine recently announced its plans to begin clinical trials using CRISPR in 2017. Two other companies – CRISPR Therapeutics and Intellia Therapeutics—are following closely behind. Researchers hope that the technique will one day be used to tackle a wide range of genetic diseases.

What are the safety concerns?

The CRISPR technology is currently imperfect, as it occasionally results in DNA cuts and changes that weren’t intended. Many scientists warn of several barriers that need to be overcome before CRISPR can be used safely and efficiently in a clinical setting. Researchers are still working on improving the efficiency of the editing process (i.e. increasing the rates of editing) and ensuring that undesirable alterations to other parts of the genome are not made. Even rare occurrences of Cas9’s off-target snips can be very problematic. For example, incorrect manipulations can accelerate a cell’s growth and lead to cancer.

Why is this technology so controversial?

Researchers, including Jennifer Doudna of UC Berkeley, who co-invented the CRISPR technology, are concerned about attempts to make genetic modifications to viable human embryos. In other words, it is theoretically possible to modify genetic material that codes hereditary characteristics, potentially giving people the power to control specific traits passed down to children.

This issue raises many safety and ethical considerations. First, an attempt to correct one gene could result in an error that leads to an unanticipated change in another. Depending on where this error takes place, the mistake could be passed down to the child’s offspring and multiple generations may face the consequences. Second, parents who manipulate their child’s genome may be making decisions that the child may not have wanted. The Center for Genetics and Society recently released a briefing of seven key dangers of genetically modified humans.

As of today, many unanswered questions remain. While this powerful new technology is undoubtedly revolutionary and holds enormous potential for the future, researchers emphasize the need to keep expectations under control.